What are the differences in management between Type 2B and Type 2M von Willebrand disease?

Management Differences Between Type 2B and Type 2M von Willebrand Disease

VWF-containing factor concentrates are recommended for Type 2B von Willebrand disease, while desmopressin may be used for Type 2M, as Type 2B patients can experience worsening thrombocytopenia with desmopressin. 1, 2

Laboratory Characteristics and Diagnosis

Type 2B and Type 2M von Willebrand disease (VWD) share some laboratory findings but have crucial differences:

• Common features 1:

  • VWF:RCo <30 IU/dL
  • VWF:Ag 30-200 IU/dL
  • VWF:RCo/VWF:Ag ratio <0.5-0.7

• Key differences:

  • Type 2B: Loss of high molecular weight multimers; enhanced ristocetin-induced platelet aggregation (RIPA) at low doses 1
  • Type 2M: Normal multimer pattern; often normal RIPA at low doses 1
  • Type 2B: Often associated with thrombocytopenia (67.2% of patients), which can fluctuate and worsen during stress 3

Treatment Approach

Type 2B VWD Management

1. First-line treatment: VWF-containing factor concentrates 1, 2

   • Desmopressin is contraindicated or used with extreme caution due to risk of worsening thrombocytopenia 4, 2, 5
   • FDA specifically warns about increased risk of thrombosis in Type 2B patients treated with desmopressin 4

2. Monitoring considerations:

   • Regular platelet count monitoring is essential 3
   • Platelet counts may decrease dramatically during pregnancy, especially in the third trimester 3
   • Postpartum hemorrhage risk is high (occurred in 5 of 8 deliveries in one study) despite prophylactic treatment 3

3. Special situations:

   • Surgical procedures require target VWF activity ≥50 IU/dL 1
   • Pregnancy requires close monitoring with target VWF:RCo ≥50 IU/dL for vaginal delivery and ≥80 IU/dL for cesarean section 1
   • Platelet transfusions may provide suboptimal results as transfused platelets may aggregate due to abnormal VWF 2

Type 2M VWD Management

1. Treatment options:

   • Desmopressin may be effective and can be used as first-line therapy in many cases 1, 6
   • VWF-containing factor concentrates are used when desmopressin is ineffective 1

2. Monitoring considerations:

   • Monitor for hyponatremia with desmopressin use 4
   • Measure serum sodium within 1 week and approximately 1 month after starting desmopressin therapy 4

3. Special situations:

   • Same surgical and pregnancy targets as Type 2B (VWF activity ≥50 IU/dL for surgery, VWF:RCo ≥50 IU/dL for vaginal delivery) 1

Potential Complications and Pitfalls

• Type 2B-specific complications:

  • Thrombocytopenia that worsens with stress, pregnancy, or desmopressin 5, 3
  • Possible thrombotic events (rare but reported) 7
  • Postpartum hemorrhage risk despite prophylaxis 3

• Common pitfalls:

  • Misdiagnosis between subtypes due to overlapping laboratory findings
  • Inappropriate use of desmopressin in Type 2B patients
  • Failure to monitor platelet counts in Type 2B patients
  • Inadequate prophylaxis for surgical procedures or delivery

Treatment Algorithm

1. Confirm VWD subtype through laboratory testing (VWF:RCo, VWF:Ag, multimer analysis, RIPA)

2. For Type 2B VWD:

   • Use VWF-containing factor concentrates for bleeding episodes and prophylaxis
   • Avoid desmopressin
   • Monitor platelet counts regularly, especially during stress, pregnancy
   • Consider adjunctive treatments like antifibrinolytics for minor bleeding

3. For Type 2M VWD:

   • Trial of desmopressin (with monitoring for response and hyponatremia)
   • If ineffective, switch to VWF-containing factor concentrates
   • Consider adjunctive treatments like antifibrinolytics

4. For both types during surgery:

   • Maintain VWF:RCo >50 IU/dL
   • Monitor VWF:RCo and FVIII:C levels at 12-24 hours post-surgery
   • Maintain VWF:RCo >50 IU/dL for 72 hours after major surgery